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Linkage disequilibrium mapping in isolated populations provides a powerful tool for fine structure localization of disease genes. Here, Luria and Delbrück's classical methods for analysing bacterial cultures are adapted to the study of human isolated founder populations in order to estimate (i) the recombination fraction between a disease locus and a marker; (ii) the expected degree of allelic homogeneity in a population; and (iii) the mutation rate of marker loci. Using these methods, we report striking linkage disequilibrium for diastrophic dysplasia (DTD) in Finland indicating that the DTD gene should lie within 0.06 centimorgans (or about 60 kilobases) of the CSF1R gene. Predictions about allelic homogeneity in Finland and mutation rates in simple sequence repeats are confirmed by independent observations.

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